CLASSES

Influenza Vaccines

DEA CLASS

Rx

DESCRIPTION

Inactivated influenza vaccine (IIV)Used to confer immunity against 3 (2 type A and 1 type B) or 4 (2 type A and 2 type B) strains likely to circulate during annual flu seasonAnnual immunizations required; recommended for all people at least 6 months of age

DOSAGE & INDICATIONS

For annual seasonal influenza prophylaxis.

Intramuscular dosage (Fluzone High-Dose)

Geriatric 65 years and older

0.5 mL IM as a single dose. Each 0.5 mL dose of Fluzone High-Dose contains influenza split virus antigens that are formulated to contain a total of 180 mcg of influenza virus hemagglutinin, 60 mcg each from the 3 influenza virus strains in the vaccine. In one study, Fluzone-High Dose showed statistical superiority to Fluzone in reducing the incidence of influenza-like illness among patients 65 years of age and older [relative efficacy 24.2% (95% CI 9.7; 36.5)].

Intramuscular dosage (Fluad)

Geriatric 65 years and older

0.5 mL IM as a single dose.

Intramuscular dosage (Fluzone Trivalent and Quadrivalent)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Children 3 to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Infants and Children 6 to 35 months

0.25 mL IM. For infants and children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.25 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Intramuscular dosage (Fluarix Quadrivalent)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Infants and Children 6 months to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Intramuscular dosage (Flulaval Quadrivalent)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Infants and Children 6 months to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Intramuscular dosage (Afluria)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Children 5 to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Intramuscular dosage (Fluvirin, Flucelvax Quadrivalent)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Children 4 to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

Intramuscular dosage (Afluria Quadrivalent)

Adults

0.5 mL IM as a single dose.

Children and Adolescents 9 years and older

0.5 mL IM as a single dose.

Children 5 to 8 years

0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2017, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2017, receive only 1 dose for 2017 to 2018. The two previous doses need not have been given during the same season or consecutive seasons.

6 to 11 months: 0.25 mL/dose IM for Fluzone; 0.5 mL/dose IM for Flulaval and Fluarix. Safety and efficacy of IM Fluvirin, Fluzone High-Dose, Agriflu, Flublok, Flucelvax, Afluria, and intradermal administration have not been established.1 to 5 months: Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

For storage information, see the specific product information within the How supplied section.

NOTE: According to U.S. federal laws, the healthcare provider must record in the patient's permanent record: the manufacturer, lot number, date of administration, and the name and address of the person administering the vaccine.Obtain a patient's current health status and immunization history to determine vaccine adverse reactions. Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967. Depending on the adverse reaction, subsequent vaccination, if needed, may be contraindicated.The health care professional should have immediate availability of epinephrine injection and other agents used in the treatment of anaphylaxis in the event of a serious allergic reaction.Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. The vaccine cannot cause influenza.Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization; materials are free of charge from the Centers for Disease Control. Provision of the Vaccine Information Statements is required by the National Childhood Vaccine Injury Act of 1986.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.Do not mix with any other vaccine.When concomitant administration of other vaccines is required, they should be given with different syringes and at different injection sites.

Intramuscular Administration

Prior to administration, clean skin over the injection site with a suitable cleansing agent.For products supplied as a suspension, shake well immediately before use.For vials, use a sterile syringe and needle to withdraw vaccine from vial. It is recommended that small syringes (0.5 mL) be used to minimize product loss. For prefilled syringes, attach a sterile needle.For adults and older children, a needle length >= 1 inch can be considered; needles < 1 inch might be of insufficient length to penetrate muscle tissue in certain adults and children.For children >= 3 years, the needle size required for deltoid injection ranges from 5/8- to 1-inch.For children 1 to 2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90 degree angle.For the majority of infants < 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.Inject into the anterolateral aspect of the mid-thigh (for infants < 1 year of age) or the deltoid muscle of the upper arm (for children and adults). Do NOT administer in the gluteal muscle. Aspirate prior to injection to avoid injection into a blood vessel. If a vessel is penetrated, withdraw the needle and use a new syringe and needle at a different injection site.Doses from Afluria vials may be administered to adults (18 to 64 years) using the PharmaJet Stratis needle-free injection system. This spring loaded device delivers a single IM dose by creating a narrow fluid stream that rapidly penetrates the skin. Safety and efficacy of needless injectors have not been established in geriatric (> 64 years) nor pediatric (< 18 years) patients.Storage of opened vials: Acceptable storage varies depending on vaccine formulation and brand. See How Supplied section or directly contact the manufacturer for specific vaccine being used.

Other Injectable Administration

Intradermal administration (Fluzone Intradermal only):Gently shake the device and remove the needle cap.Insert the needle perpendicular to the skin in the region of the deltoid. Maintain light pressure on the surface of the skin and push the plunger to inject the dose. Do not aspirate.After needle removal from the skin, firmly push the plunger to activate the needle shield.

STORAGE

Afluria :- Discard entered multi-dose vial after 28 days- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)Agriflu:- Do not freeze- Protect from light- Store between 36 to 46 degrees FAlfuria:- Discard entered multi-dose vial after 28 days- Discard if product has been frozen- Do not freeze- Protect from light- Store between 36 to 46 degrees FFLUAD:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)- Store in original package until time of useFluarix:- Discard if product has been frozen- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)- Store in original containerFluarix Quadrivalent:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)- Store in original package until time of useFlublok:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Store between 36 to 46 degrees FFlublok Quadrivalent:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Store between 36 to 46 degrees FFLUCELVAX:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)Flulaval:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)- Store in original containerFluvirin:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Refrigerate (between 36 and 46 degrees F)- Store in original package until time of useFluzone:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Store between 35 to 46 degrees FFluzone High-Dose:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Store between 35 to 46 degrees FFluzone Intradermal:- Discard if product has been frozen- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Store between 35 to 46 degrees F

CONTRAINDICATIONS / PRECAUTIONS

General Information

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of influenza virus vaccine, inactivated has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1—800—822—7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Intravenous administration, subcutaneous administration

Influenza virus vaccine should not be given via intravenous administration or subcutaneous administration, it is for intramuscular (IM) administration only, with the exception of the intradermal Fluzone products. All other formulations should not be given by intradermal administration. Incorrect administration may result in inadequate immunity.

Fever, respiratory infection

The decision to administer or to delay vaccination with the influenza virus vaccine because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved, unless the patient is at immediate risk of infection. Use caution when administering the vaccine to patients with severely compromised cardiopulmonary status. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

All formulations of the inactivated influenza vaccine (IIV), with the exception of Flucelvax and Flublok, are contraindicated by the manufacturer for use in persons with a known history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine or any of its components, persons who have had a life-threatening reaction to any previous influenza vaccination, or persons with egg hypersensitivity. Agriflu is also contraindicated in persons with kanamycin hypersensitivity and/or neomycin hypersensitivity. Due to differences in manufacturing processes, Flucelvax and Flublok do not use eggs to propagate the virus; thus, they are only contraindicated in persons with a known history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine or any of its components. Flucelvax, however, cannot be considered 100% egg-free because the initial seed virus is created using reference virus stains from the World Health Organization, which have been passaged in eggs. The Advisory Committee on Immunization Practices (ACIP) recommends administering any licensed influenza vaccine (i.e., any IIV or recombinant influenza vaccine (RIV)) to patients with egg allergy of any severity. Patients who have had symptoms other than urticaria after egg exposure (i.e. angioedema, respiratory distress, lightheadedness, or recurrent emesis) or required emergency medical intervention, may also receive any IIV or RIV vaccine; however, it is recommended that the vaccine only be administered in an inpatient or outpatient medical setting by a health care provider experienced in the recognition and management of severe allergic conditions. Although no specific observation time is recommended for egg-allergic patients, ACIP recommends patients be observed for syncope for 15 minutes after vaccination. Influenza vaccine is not recommended for patients with a history of severe allergic reaction to the vaccine. The American Academy of Pediatrics (AAP), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI) do not recommend any special precautions for egg-allergic recipients, regardless of severity. The AAAAI and ACAAI considers any special precautions (i.e., special observation periods or administration in a specialized medical setting) unnecessary due to the extremely rare risk of anaphylactic reactions after vaccination. They recommend that providers and screening questionnaires not ask about the egg allergy status of the influenza virus vaccine recipient. As with any biologic product, the prescriber or health care professional should have procedures in place to manage allergic reactions. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the influenza virus vaccine. Additionally, caution must be exercised when using any Agriflu, Flucelvax, Fluad, and Fluvirin prefilled syringes, as the tip caps may contain natural latex rubber which may cause reactions in patients with latex hypersensitivity. Latex is not contained in Fluarix Trivalent or Quadrivalent, Flucelvax Quadrivalent, the vial stoppers of Fluvirin, Flublok, Flulaval Trivalent or Quadrivalent, nor in any Fluzone or Afluria products.

Guillain-Barre syndrome

Persons with a history of Guillain-Barre syndrome (GBS) have a substantially greater likelihood of subsequently developing GBS than persons without such a history. Thus, the likelihood of coincidentally developing GBS after influenza vaccination is expected to be greater among persons with a history of GBS than among persons with no history of this syndrome. It is not known if influenza vaccination is causally associated with this risk for recurrence of GBS. Nevertheless, the Advisory Committee on Immunization Practices (ACIP) recommends against influenza immunization in non-high risk patients who have developed GBS within 6 weeks of a previous influenza vaccination. However, for persons with a history of GBS who are at high risk for severe complications from influenza, the benefits of the influenza vaccination may justify the risks.

Geriatric

Geriatric persons may develop lower postvaccination antibody titers than healthy young adults and, thus, may remain susceptible to influenza-related upper respiratory tract infection (see Pharmacokinetics). However, even if such persons develop influenza illness despite vaccination, the vaccine can be effective in preventing lower respiratory tract infection or other secondary complications, thereby reducing the risk for hospitalization and death. In a retrospective study of data from 1990—2000, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling patients at least 65 years of age as compared with unvaccinated patients. Specifically, vaccination was associated with a 27% reduction in the risk of hospitalization for pneumonia or influenza and a 48% reduction in the risk of death. Statistically significant reductions in the risk of both hospitalization and death were also found by sensitivity analyses, which modeled the effect of a hypothetical unmeasured confounder that would have caused overestimation of vaccine effectiveness. In elderly nursing home residents, administration of the flu vaccine annually prior to October should generally be avoided because antibody concentrations can decrease within a few months of immunization.

Children, infants

Use caution when using the Afluria formulation of inactivated influenza virus vaccine in children younger than 9 years of age. In 2010, the Southern Hemisphere 2010 Afluria formulation was associated with increased post-marketing reports of fever and febrile seizures in children predominantly below the age of 5 years as compared to previous years; accordingly, Afluria is no longer FDA approved in infants and children younger than 5 years, and no longer recommended by the ACIP in children younger than 9 years. If no other licensed inactivated vaccine is available and the child has a medical condition that may increase the risk of influenza complications, Afluria may be used. During the 2010/2011 influenza season, increases in reports of febrile seizures in children 6 months to 4 years of age (most commonly in children 12 to 23 months of age) receiving the inactivated influenza vaccine and the conjugated pneumococcal vaccine (Prevnar 13) concomitantly occurred. Data from the 2011/2012 influenza season (which used the same formulation as the 2010/2011 season) resulted in similar findings; however, an increased risk for febrile seizures was not observed during the 2012/2013 influenza season. Although this observational data may suggest association of the seizure with the simultaneous administration of the vaccines, immunization should not be delayed (e.g., by separating administration across multiple healthcare visits) due to the threat of disease.

Pregnancy

No adequate and well-controlled studies have been conducted in pregnant women and the ability of the vaccine to cause fetal harm or to affect reproductive capacity is unknown. During animal studies, no evidence of impaired fertility or fetal harm was noted with Afluria, Agriflu, Fluarix, Flublok, Flucelvax, FluLaval, Fluvirin, or Fluzone Quadrivalent or Intradermal. Pregnancy may increase the risk of serious medical complications from influenza. It is estimated that 12 hospitalizations among pregnant women could be prevented for every 1,000 pregnant women who are vaccinated. Therefore, the Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or will be pregnant (in any trimester) during the influenza season be routinely vaccinated with an inactivated influenza vaccine (vs. live-attenuated influenza vaccine). Although more data are needed, studies of more than 2,000 pregnant women have demonstrated no adverse fetal effects associated with influenza virus vaccine. Many experts consider influenza vaccination safe during any stage of pregnancy. However, because spontaneous abortion is common in the first trimester and unnecessary drug-exposures have traditionally been avoided during this time, some experts prefer waiting until the second trimester of pregnancy to vaccinate. In addition to benefits to the mother, influenza vaccine administration during pregnancy appears to help protect newborns and infants. Fewer cases of laboratory-confirmed influenza occurred during the first 6 months of life among infants of the 159 mothers who received the inactivated influenza vaccine (6 cases) as compared with infants of 157 mothers who received the pneumococcal polysaccharide vaccine (16 cases). The clinical judgment of the physician is paramount in the determination of whether to vaccinate a pregnant woman. GlaxoSmithKline (GSK), the manufacturer of FluLaval and Fluarix, and Sanofi Pasteur, the manufacturer of Fluzone, have established pregnancy registries to monitor pregnancy outcomes and newborn health following vaccination. Patients who receive these vaccines during pregnancy are encouraged to contact GSK by telephone at 888 - 452 - 9622 or Sanofi Pasteur at 800 - 822 - 2463.

Breast-feeding

Data are limited regarding use of the influenza virus vaccine during breast-feeding and its' excretion in human breast milk is unknown. The manufacturers recommend caution when administering to nursing mothers; however according to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk for mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

Patients with thrombocytopenia or a coagulopathy (e.g., hemophilia), vitamin K deficiency, or who are on anticoagulant therapy should be monitored closely when given influenza virus vaccine because bleeding can occur at the IM injection site.

Patients with significant immunosuppression may not have an adequate antibody response to the influenza virus vaccine. Immunosuppressed persons may include patients with severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (< 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with influenza virus vaccine within 2 weeks before starting immunosuppressive therapy or while receiving immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after therapy is discontinued if immune competence has been restored. Although patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) could have a diminished response, 1 randomized, placebo controlled trial noted that the administration of influenza virus vaccine was highly effective in preventing hospitalization due to influenza in patients with HIV infection and was not associated with changes in viral load or CD4 counts (mean count 400 cells/mm3). The CDC recommends immunization of HIV-infected individuals with the inactivated vaccine, as this measure is safe and may confer protection against influenza. Inactivated influenza vaccination should be offered to all patients with HIV infection. However, because of the theoretical concern that increases in HIV plasma RNA following vaccination during pregnancy might increase the risk of perinatal transmission of HIV, providers may wish to defer vaccination for HIV-positive pregnant patients until after HAART is initiated.

Syncope

Injectable vaccines, including influenza virus vaccine, have been associated with episodes of syncope and fainting. These events may be accompanied by transient tonic-clonic limb movements, visual disturbances, and paresthesias. Prior to administration, ensure procedures are in place to prevent falls and restore cerebral perfusion. Monitor vaccine recipients after administration of the dose. If syncope occurs, place the patient in a supine or Trendelenburg position to restore cerebral perfusion.

DRUG INTERACTIONS

Adalimumab: (Major) It is not clear if adalimumab interferes with the effectiveness of influenza virus vaccine. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients receiving such therapies. Carbamazepine: (Minor) The elimination of some medications that are metabolized by cytochrome P-450, including carbamazepine, may be altered following administration of influenza virus vaccine. Reports concerning impaired drug clearance and possible toxicity are conflicting, and the clinical importance of the potential interaction is not clear. Fosphenytoin: (Minor) Although influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including phenytoin (or fosphenytoin), the reports concerning possible toxicity are conflicting. Most recent reports have noted no adverse clinical outcomes from the use of influenza virus vaccine in patients taking these medications; the use of these medications should not prohibit influenza immunization if indicated. Isolated reports of increased or decreased phenytoin serum concentrations secondary to the administration of influenza virus vaccine exist, but these interactions appear to be rare. Interactions, when they occur, are usually noted between 7 and 14 days post-vaccination. Although not routinely expected, it may be prudent to inform patients of how to recognize and manage the symptoms of phenytoin toxicity or the symptoms of decreased phenytoin efficacy after receiving flu vaccination. Phenytoin: (Minor) Although influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including phenytoin, the reports concerning possible toxicity are conflicting. The use of these medications should not prohibit influenza immunization if indicated. Theophylline, Aminophylline: (Minor) Influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including theophylline or aminophylline. The use of these medications should not prohibit influenza immunization if indicated. However, because an occasional predisposed patient may experience an increase in the effects of theophylline or aminophylline, monitoring for theophylline toxicity may be warranted; a temporary dosage adjustment may be needed if an interaction occurs.

PREGNANCY AND LACTATION

Pregnancy

No adequate and well-controlled studies have been conducted in pregnant women and the ability of the vaccine to cause fetal harm or to affect reproductive capacity is unknown. During animal studies, no evidence of impaired fertility or fetal harm was noted with Afluria, Agriflu, Fluarix, Flublok, Flucelvax, FluLaval, Fluvirin, or Fluzone Quadrivalent or Intradermal. Pregnancy may increase the risk of serious medical complications from influenza. It is estimated that 12 hospitalizations among pregnant women could be prevented for every 1,000 pregnant women who are vaccinated. Therefore, the Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or will be pregnant (in any trimester) during the influenza season be routinely vaccinated with an inactivated influenza vaccine (vs. live-attenuated influenza vaccine). Although more data are needed, studies of more than 2,000 pregnant women have demonstrated no adverse fetal effects associated with influenza virus vaccine. Many experts consider influenza vaccination safe during any stage of pregnancy. However, because spontaneous abortion is common in the first trimester and unnecessary drug-exposures have traditionally been avoided during this time, some experts prefer waiting until the second trimester of pregnancy to vaccinate. In addition to benefits to the mother, influenza vaccine administration during pregnancy appears to help protect newborns and infants. Fewer cases of laboratory-confirmed influenza occurred during the first 6 months of life among infants of the 159 mothers who received the inactivated influenza vaccine (6 cases) as compared with infants of 157 mothers who received the pneumococcal polysaccharide vaccine (16 cases). The clinical judgment of the physician is paramount in the determination of whether to vaccinate a pregnant woman. GlaxoSmithKline (GSK), the manufacturer of FluLaval and Fluarix, and Sanofi Pasteur, the manufacturer of Fluzone, have established pregnancy registries to monitor pregnancy outcomes and newborn health following vaccination. Patients who receive these vaccines during pregnancy are encouraged to contact GSK by telephone at 888 - 452 - 9622 or Sanofi Pasteur at 800 - 822 - 2463.

Data are limited regarding use of the influenza virus vaccine during breast-feeding and its' excretion in human breast milk is unknown. The manufacturers recommend caution when administering to nursing mothers; however according to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk for mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Influenza virus vaccine imparts immunity against the influenza virus by stimulating production of antibodies that are specific to the disease. Vaccine recipients develop immunity only to those strains of the virus from which the vaccine was prepared. Influenza viruses are recognized by the surface antigens they carry, and two such antigens, hemagglutinin (H) and neuraminidase (N) have been identified and are used to classify the various viruses. Subtypes of these strains (H1, H2, H3, N1, N2) are associated with influenza A virus and have been recognized to cause disease in humans. Immunity to these surface antigens increases resistance to infection and decreases the severity of the disease if infection occurs. Eventually, antigenic variation can occur, and immunity to one strain may no longer impart immunity to distantly related subtypes of the virus. Influenza B viruses also exhibit antigenic variation, and new variants of both types of viruses continue to cause widespread epidemics of respiratory disease.

PHARMACOKINETICS

The inactivated influenza virus vaccine (IIV) is usually administered intramuscularly; intradermal vaccines are also available. The vaccine usually imparts a protective effect within 10 to 14 days of administration. Post-vaccine antibody titers are generally high enough in healthy young adults and children to provide resistance against infection by strains found in the vaccine as well as related strains. A hemagglutination-inhibiting antibody titer of at least 1:40 may be protective against influenza infection in up to 50% of people. Among 1007 patients 18 to 64 years of age who got Afluria, 94.2 to 99.9% had a postvaccination titer of at least 1:40. The duration of immunity imparted by the influenza vaccine generally lasts 6 to 12 months.

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